Using extensive in vitro manipulations, previous investigators have reported increased erythrocyte Na content and several abnormalities of erythrocyte Na transport in essential hypertension (HT). Because of the in vitro conditions and separation of red cells from plasma, the in vivo significance and the role of circulating humoral agents in the pathogenesis of the reported abnormalities cannot be evaluated. The purpose of this proposal is two-fold: 1. to study erythrocyte Na content and transport in human HT under experimental conditions which approximate in vivo conditions: and 2. to investigate the role of plasma factors in the pathogenesis of the reported abnormalities of erythrocyte Na transport. In white, male untreated hypertensive and normotensive control subjects, erythrocyte Na and K concentration (Na and Ki) will be measured by immediate centrifugation of whole blood over oil to separate the cells from plasma. I125-albumin and CO57-EDTA will be used to estimate plasma trapping. The presence of white cells and platelets in the cell pellet has no effect on erythrocyte cation measurements. To estimate Na-K pump activity, erythrocyte Rb86 uptake will be measured in the subjects' own plasma with or without the addition of 1 mM ouabain. To investigate the role of plasma factors, type O donor erythrocytes will be incubated in the plasma of hypertensive and normotensive subjects followed by measurements of intracellular cation concentrations and Na-K pump activity. Preliminary results indicate that "in vivo" Na-i is reduced and Ki is increased in human HT. It is postulated that through activation of the ouabain-sensitive Na-K pump, a long-acting plasma factor is responsible for the findings.